Buccafusco Jerry J, Terry Alvin V
Alzheimer's Research Center, Medical College of Georgia, Augusta, GA 30912, USA.
J Mol Neurosci. 2004;24(1):85-91. doi: 10.1385/JMN:24:1:085.
Donepezil (Aricept), a long-acting cholinesterase inhibitor, is widely used in the treatment of Alzheimer's disease to improve cognition and memory. Many drugs within the class of cognition-enhancing agents, both currently approved medications and those under development, have clinical indications narrowly relegated to Alzheimer's disease. The purpose of this study was to determine whether the efficacy attributed to donepezil in its ability to improve delayed matching accuracy by monkeys was independent of age. Male and female rhesus monkeys (n = 17) ranging from 9to 29 yr of age were administered donepezil (10, 25, 50, and 100 microg/kg, im) during 4 discrete test days. Donepezil treatment improved average task accuracy, but intersubject variability prohibited statistical significance. When animals were considered individually, the most effective dose of donepezil was associated with a highly significant increase in group task performance that was consistent with enhanced recall during testing. The variability associated with the dose-response analysis was attributable primarily to subject age, such that older monkeys required higher doses of donepezil. Yet at doses that were effective in all subjects, there was no relationship between age and the improvement in task accuracy. Likewise, there was no association between baseline task proficiency and improvement in task accuracy.
多奈哌齐（安理申）是一种长效胆碱酯酶抑制剂，广泛用于治疗阿尔茨海默病以改善认知和记忆。许多认知增强剂类药物，包括目前已获批的药物和正在研发的药物，其临床适应症都局限于阿尔茨海默病。本研究的目的是确定多奈哌齐提高猴子延迟匹配准确性的功效是否与年龄无关。在4个不同的测试日，对17只年龄在9至29岁之间的雄性和雌性恒河猴给予多奈哌齐（10、25、50和100微克/千克，肌肉注射）。多奈哌齐治疗提高了平均任务准确性，但个体间的变异性使得结果无统计学意义。当单独考虑动物时，多奈哌齐最有效的剂量与组任务表现的显著提高相关，这与测试期间回忆能力增强一致。剂量反应分析中的变异性主要归因于动物年龄，即年龄较大的猴子需要更高剂量的多奈哌齐。然而，在对所有动物都有效的剂量下，年龄与任务准确性的提高之间没有关系。同样，基线任务熟练程度与任务准确性的提高之间也没有关联。
